U.S. patent application number 09/732211 was filed with the patent office on 2001-06-21 for apparatus and method for rapid spectrophotometric pre-test screen of specimen for a blood analyzer.
Invention is credited to Cadell, Theodore E., Samsoondar, James.
Application Number | 20010004285 09/732211 |
Document ID | / |
Family ID | 22085014 |
Filed Date | 2001-06-21 |
United States Patent
Application |
20010004285 |
Kind Code |
A1 |
Cadell, Theodore E. ; et
al. |
June 21, 2001 |
Apparatus and method for rapid spectrophotometric pre-test screen
of specimen for a blood analyzer
Abstract
A method and apparatus for use in respect of samples which are
assessed for quality prior to testing in a clinical analyzer. The
method and apparatus identify parameters such as gel level and
height of fluid above the gel in blood samples, where appropriate,
for the purposes of positioning the specimen for determination of
interferents. Such interferents include hemoglobin (Hb), total
bilirubin and lipids. These interferents are determined by
measurement of absorption of different wavelengths of light in
serum or plasma, or other speciments, which are then compared with
values obtained through calibration using reference measurements
for the respective interferents in serum or plasma or other type of
specimen. Determination of temperature of the specimen, as well as
specimen type, for example whether the specimen is urine or plasma
or serum, may also be carried out.
Inventors: |
Cadell, Theodore E.;
(Conestogo, CA) ; Samsoondar, James; (Cambridge,
CA) |
Correspondence
Address: |
H. Roger Hart
Bereskin & Parr
40 King Street West
Box 401
TORONTO
ON
M5H 3Y2
CA
|
Family ID: |
22085014 |
Appl. No.: |
09/732211 |
Filed: |
December 8, 2000 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09732211 |
Dec 8, 2000 |
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09068835 |
Feb 8, 1999 |
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6195158 |
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Current U.S.
Class: |
356/39 |
Current CPC
Class: |
G01N 21/3103
20130101 |
Class at
Publication: |
356/39 |
International
Class: |
G01N 033/48 |
Claims
We claim:
1. An apparatus for monitoring a specimen before said specimen is
presented for clinical analysis, said apparatus comprised of: a)
means for holding a specimen container wherein said means and said
container have a longitudinal axis; b) a first radiation source
disposed to direct radiation at said specimen and a first radiation
detector disposed to allow collection of transmitted or reflected
radiation from said specimen; c) electrical means to couple said
first radiation source to an electronic driver; d) electrical means
to couple said first radiation detector to a computing means which
analyzes output from said detector for determination of at least
one parameter about said specimen; e) means to position said
container in said axis of said holder based on results from said
analysis; f) a second radiation source; g) means to transmit
radiation from said second radiation source to said specimen; h)
means to spectrophotometrically detect transmitted or reflected
radiation from said specimen; and i) means for correlating said
detected radiation to determine the concentration of at least one
interferent in said specimen.
2. The apparatus of claim 1 wherein said specimen is one of the
group consisting of blood, serum, plasma or urine.
3. The apparatus of claim 1 wherein said first radiation source is
comprised of a linear array of LEDs disposed along one side of said
axis of said container and said first radiation detector is
comprised of a corresponding array of silicon detectors on the
opposite side of the container to collect transmitted radiation and
wherein a spectrophotometer provides the second radiation source
and detectors.
4. The apparatus of claim 1 further comprising one or more lenses
to focus said radiation from said first radiation source to spread
said radiation across said axis of said container, and further
wherein said apparatus contains one or more further lenses which
collect transmitted or reflected radiation from said specimen and
direct it to said spectrophotometric radiation detector.
5. The apparatus of claim 3 or 4 wherein said specimen container
contains a sample identification label on the exterior surface of
said container.
6. The apparatus of claim 3 or 4 wherein said first radiation and
radiation from said spectrophotometer is transmitted through a
label, a container and a specimen.
7. A method for monitoring specimens before said specimens are
presented for clinical analysis comprising the steps of: a) placing
a specimen in a specimen container; b) placing said specimen
container into a holding means; c) applying radiation from a first
radiation source to said specimen and collecting transmitted or
reflected radiation from said specimen; d) analyzing said collected
radiation to determine at least one parameter about said specimen;
and e) based on results from said one or more determinatioi is,
positioning said container in said holder for further analysis
wherein said further analysis comprises the steps of: (i)
spectrophotometrically applying radiation from a second radiation
source to said specimen and detecting transmitted or reflected
radiation from said specimen; and (ii) correlating said
spectrophotometrically detected radiation to determine the
concentration of at least one interferent in said specimen.
8. The method of claim 7 wherein said container has a longi'Wdinal
axis and said radiation from said first radiation source is
focussed through one or more lenses to spread said radiation across
said axis of said container, said radiation being transmitted
through said container and wherein reflected or transmitted
radiation from said container is passed through one or more lenses
and thereby directed to said radiation detector.
9. The method of claim 7 wherein said container has a longitudinal
axis and said radiation from said first radiation source is applied
through a linear array of LEDs disposed along on one side of said
axis of said container and said transmitted or reflected radiation
is collected by a corresponding array of silicon detectors on the
opposite side of said container.
10. The method of claim 8 or 9 wherein said specimen is one of the
group consisting of blood, serum, plasma or urine.
11. The method of claim 8 or 9 where said specimen container
contains a sample identification label on the exterior surface of
said container and said radiation from said first and second
radiation sources is transmitted through said label, container and
specimen.
12. The method of claim 8 or 9 wherein a bar code is present on
said container and said bar code is read to identify said
specimen.
13. The method of claim 7, 8 or 9 wherein the parameter determined
is one or more of the group consisting of a gel level, the
thickness of said gel, the height of fluid above said gel, and the
volume of fluid above said gel.
14. The method of claim 7, 8 or 9 wherein said
spectrophotometrically detected radiation is used to determine the
concentration of one or more of the group consisting of hemoglobin,
total bilirubin, unconjugated bilirubin, conjugated bilirubin,
delta bilirubin, biliverdin, and lipid.
15. The method of claim 14 wherein said spectrophotometrically
detected radiation is used to determine the temperature of said
specimen.
16. The method of claim 14 wherein said spectrophotometrically
detected radiation is used to determine the type of said
specimen.
17. A method for monitoring blood specimens in S'P-ecimen
containers before said specimens are presented for clinical
analysis comprising the steps of: a) reading any bar code on said
container; b) determining the location of a gel level of said
specimen and the height of any fluid located above said gel c) on
the basis of said determination positioning said container such
that spectral data can be obtained; and d) interpreting said
spectral data to determine the concentration of one or more
intereferents, and specimen type and specimen temperature.
18. The method of claim 17 wherein said determinations are made
when said container has a label on the exterior surface of said
container and said determinations are made through said label.
19. The method of claim 17 wherein said interferents are selected
from the group consisting of hemoglobin, total bilirubin,
unconjugated bilirubin, conjugated bilirubin, delta bilirubin,
biliverdin, and lipid.
20. A method of determining the hematocrit of a blood sample
comprising the steps of: a) centrifuging a whole blood sample in a
tube having an axis, to separate the sample into two phases, one
being the blood cells and the other the serum or plasma; b) while
maintaining said phases separate, optically scanning the phases in
said tube along said tube axis to determine a length of said axis
that each of said phases occupies; c) calculating the ratio of the
axis length amounts of the cellular phase and of the serum or
plasma phase; and d) converting said ratio to hematocrit value.
Description
RELATED APPLICATION INFORMATION
[0001] This is a divisional application of U.S. patent application
Ser. No. 09/068,835 filed Feb. 8, 1999.
TECHNICAL FIELD
[0002] This invention relates to spectrophotometry and the
spectrophotometric analysis of blood samples. In particular, this
invention relates to a method and apparatus for providing a rapid
pre-test determination of interferent concentration, specimen type
and physical properties of a blood sample for a blood analyzer by
measurement of absorbance or reflectance.
BACKGROUND ART
[0003] Clinical laboratory tests are routinely performed on the
serum or plasma of whole blood. In a routine assay, red blood cells
are separated from plasma by centrifugation, or red blood cells and
various plasma proteins are separated from serum by clotting prior
to centrifugation.
[0004] Haemoglobin (Hb), bilirubin (Bili) and light-scattering
substances like lipid particles are typical substances which will
interfere with, and affect spectrophotometric and other blood
analytical measurements. Such substances are referred to as
interferents.
[0005] Many tests conducted on plasma or serum samples employ a
series of reactions which terminate after the generation of
chromophores which facilitate detection by spectrophotometric
measurements at one or two wavelengths. Measurement of interfering
substances prior to conducting such tests is important in providing
meaningful and accurate test results. In fact if a sample is
sufficiently contaminated with interferents, tests are normally not
conducted as the results will not be reliable.
[0006] In analytical laboratories bar codes are increasingly being
used to identify samples, and such laboratories routinely analyze a
variety of biologic fluids, for example, the most common being
blood and urine.
[0007] Specimen integrity directly affects the accuracy of test
results. Numerous factors can compromise specimen integrity such
as, having the right sample, e.g., blood rather than urine; in the
case of a blood sample, whether it is serum or plasma; the presence
of interferents in a plasma or serum sample; the volume of the
sample; the sample temperature; and the location of the upper
surface of a gel barrier, which is also referred to herein as the
gel level, in a blood sample, where the gel is an inert material
used to separate serum or plasma from clotted or packed blood
bells, respectively. Finally, it is critical that the sample tested
be properly matched to the results of any assessments on the
sample.
[0008] Current methods used for quality assurance and specimen
integrity rely principally on visual inspection of the specimen
with or without comparison to a reference chart, depending upon
which variable is being assessed. Visual inspection of samples is
sometimes employed on a retrospective basis where there is
disagreement between test results and clinical status of the
patient in order to help explain such discrepancies.
[0009] A sample of plasma or serum is normally transferred from the
original tube to a secondary tube. These secondary tubes may be
amber coloured to protect photo sensitive constituents. Amber
colouring makes visual inspection virtually impossible. On
occasion, labels cover portions of the tube further restricting a
full visual examination. Further, it is sometimes difficult to
distinguish between urine and plasma or serum samples, even in
transparent tubes.
[0010] Pre-test screening of specimens by visual inspection is
semi-quantitative at best, and highly subjective and may not
provide the quality assurance required.
[0011] Furthermore, visual inspection of specimens is a time
consuming, rate limiting process. Consequently, state-of-the-art
blood analyzers in fully and semi-automated laboratories do not
employ visual inspection of specimens. However, other methods such
as direct sampling are not rapid enough or cost effective. In order
to obtain a measurement of the sample of the plasma or serum,
specimen tubes must be uncapped, a direct sample of the specimen
taken and diluted prior to measurement.
SUMMARY OF INVENTION
[0012] The disadvantages of the prior art may be overcome by
providing a rapid and accurate method and apparatus for monitoring
blood specimens before samples are presented for analysis.
[0013] In one aspect of the invention, the bar code on the specimen
tube is read to identify the specimen, as well as the bar code
reading, determination of the gel level of the specimen and the
height of fluid above the gel provide the basis for positioning the
specimen container so that spectral data can be obtained. The
spectral data is used in a novel way to determine if the specimen
which is presented for analysis contains interferents and if so, to
what extent; to determine specimen type, for example if it is urine
or plasma or serum; and to determine the temperature of the
specimen.
[0014] In another aspect of the invention, there is provided an
apparatus which incorporates: A. a device to read any bar code
present on a specimen container and thereby identify and provide
information with respect to positioning the specimen; B. a device
to determine the location of the upper surface of a gel barrier of
the specimen and the height of fluid above the gel; and C. A
spectrophotometric device to irradiate and measure radiation from
the specimen so as to determine if the specimen which is presented
for analysis contains interferents and if so, to what extent; to
determine specimen type; and to determine the temperature of the
specimen. This apparatus is capable of these determinations where
the sample tube containing the specimen has a sample identification
label on the exterior surface.
[0015] In a further aspect of the invention, there is provided a
method for the following: to read any bar code present on specimen
container and thereby identify and provide information with respect
to positioning the specimen; to determine the location of the upper
surface of a gel barrier of the specimen and the height of fluid
above the gel; to determine if the specimen which is presented for
analysis contains interferents and if so, to what extent; to
determine specimen type; and to determine the temperature of the
specimen. The method of this invention allows for these
determinations where the sample tube containing the specimen has a
sample identification label on the exterior surface.
[0016] In yet another aspect of the invention, there is provided an
apparatus and a method for the determinations described herein
where the radiation from the spectrophotometer, or other
appropriate source, is transmitted through the label, container and
specimen.
[0017] In one embodiment, the bar code reading as well as the gel
level and height of fluid above the gel are first determined. This
determination provides information essential for proper positioning
of the sample for the following determinations. The concentration
of interferents such as hemoglobin (Hb), total bilirubin
(calibrated for unconjugated bilirubin, conjugated bilirubin, delta
bilirubin, the sum of results for these three gives total
bilirubin) and lipids are determined by measurement of absorption
of different wavelengths of light in serum or plasma specimens
which are then compared with values obtained through calibration
using reference measurements for the respective interferents in
serum or plasma specimens. This is true also for determination of
temperature of the sample. A determination of specimen type, for
example whether the specimen is urine or plasma or serum, is also
made. This determination is made by recordal of spectral data for
different samples then through statistical analysis, the spectra
are classified according to sample type. In addition a bar code
reading is carried out either simultaneously, before or after the
determination of the other parameters. To those skilled in the art,
it is clear that although certain sequences of determinations are
outlined here, any combination or sequence of combinations is
within the scope of this invention.
[0018] In another embodiment, the bar code reading as well as the
gel level and height of fluid above the gel are first determined.
This determination provides information essential for proper
positioning of the sample for the following determinations. The
concentration of interferents such as hemoglobin (Hb), total
bilirubin (calibrated for unconjugated bilirubin, conjugated
bilirubin, and delta bilirubin, the sum of results for these three
gives total bilirubin) and lipids are determined by measurement of
reflectance of different wavelengths of light in serum or plasma
specimens which are then compared with values obtained through
calibration using reference measurements for the respective
interferents in serum or plasma specimens. This is true also for
determination of temperature of the sample. A determination of
specimen type, for example whether the specimen is urine or plasma
or serum, is also made. This determination is made by recordal of
spectral data for different samples then through statistical
analysis, the spectra are classified according to sample type. In
addition a bar code reading is carried out either simultaneously,
before or after the determination of the other parameters. To those
skilled in the art, it is clear that although certain sequences of
determinations are outlined here, any combination or sequence of
combinations is within the scope of this invention.
BRIEF DESCRIPTION OF DRAWINGS
[0019] FIG. 1 is a longitudinal cross-section of a sample holder
adapted for use with LED and radiation source.
[0020] FIG. 2 is a top view of the complete sample holder of FIG.
1.
[0021] FIG. 3 is a longitudinal cross-section of a sample holder
adapted for use with a laser and radiation source.
[0022] FIG. 4 is a top view of the complete sample holder of FIG.
3.
DESCRIPTION OF PREFERRED EMBODIMENTS
[0023] In operation, the apparatus first conducts a determination
of the bar code and its position on the tube, and, based on the
latter determination the tube is presented to the specimen holder 2
in a position so that the bar code does not interfere with the
measurement process.
[0024] With respect to measuring gel level and height of fluid 26
above the gel 24, the specimen is placed in a specimen holder 2 of
FIG. 1, which will also contain a linear array of LEDs 16 on one
side of the tube, and a corresponding array of silicon detectors 20
on the opposite side of the tube. The LEDs 16 are coupled by
electrical connections 6 to an electronic driver 4. The detectors
20 are coupled by electrical connections 7 to a microprocessor (not
shown) which analyzes output. The number of LEDs and detectors will
depend on the length of the tube, e.g., for a commonly used tube of
length 10 cm, 22 LEDs and 20 detectors arranged 5 mm apart will be
necessary to accommodate from a completely filled tube to an empty
tube. In operation the first detector at the top of the column
monitors as the three LED's opposite are flashed in succession: one
which is directly opposite, one 5 mm above, and one 5 mm below. The
measured distance between the LEDs and the detectors is used to
determine tube diameter. This measurement is performed
electronically, mechanically or optically, or in any combination of
these. In a preferred embodiment this measurement is performed by a
combination of mechanical and electronic operations. The fluid
volume is calculated from the measured tube diameter and the
measured height of fluid above the gel barrier.
[0025] Alternatively, with respect to measuring gel level and
height of fluid, a diode laser provides the radiation source
wherein the source is focussed through a series of lenses 30 to
spread the radiation 32 across the length of the sample tube. The
light being transmitted through the sample tube is passed through a
further series of lenses 34 and directed onto a PDA sensor 36.
Again, through this apparatus the tube is analyzed in 1 mm
increments and the results are correlated to liquid height 26 and
gel level 24. It is readily apparent that either approach also
allows for the determination of the hematocrit of any blood sample.
This is achieved by centrifuging a whole blood sample in a
container into two phases, one being the blood cells and the other
being serum or plasma. The container is then scanned by the present
invention and the length of the container that each of the phases
occupies is thereby determined. With this data the ratio of the
length amounts of the cellular phase and of the serum or plasma
phase is converted to hematocrit value.
[0026] Based upon the results from the above determinations, the
relative positions of the tube and the fibre optics can be adjusted
so as to optimize the position of the fluid compartment for
subsequent determinations. Consequently, there is space between the
walls of the sample holder 2 and the fibre optics 10 and 14 to
allow for such adjustments.
[0027] With respect to determination of sample type, temperature,
as well as for measurement of interferents, reference is made to
FIG. 2. The sample 22 is placed into a specimen holder 2 (see FIG.
1 for longitudinal view) which is located in a housing (not shown).
A radiation source 8, capable of emitting radiation in a range from
about 400 nm to 2,500 nm, is optically connected by fibre optics 10
to the sample. In operation where absorbance is measured the light
source is directed through the sample, and the transmitted
radiation is detected by a sensor 12, which is a photo diode array
(PDA), that is located opposite the source. In operation where
reflectance is measured, the detectors are proximate to the
emission source (not shown). In both cases the detector is
optically connected by fibre optics 14, or any other suitable
means. In this apparatus the radiation source is split so that
there is a reference beam which by-passes the sample. The apparatus
also contains a means for correlating a sensor response, from the
sample path relative to a sensor response from the reference path,
to a quantity of a known substance in said sample. The housing has
a cavity for receiving a sample and a lid for selectively opening
and closing the cavity. The radiation source is for emitting a beam
of radiation, and the sensor is responsive to receipt of
radiation.
[0028] While the invention has been particularly shown and
described with reference to certain embodiments, it will be
understood by those skilled in the art that various other changes
in form and detail may be made without departing from the spirit
and scope of the invention.
* * * * *